Organoids form through poorly understood morphogenetic processes in which initially homogeneous ensembles of stem cells spontaneously self-organize in suspension or within permissive three-dimensional extracellular matrices. Yet, the absence of virtually any predefined patterning influences such as morphogen gradients or mechanical cues results in an extensive heterogeneity. Moreover, the current mismatch in shape, size and lifespan between native organs and their in vitro counterparts hinders their even wider applicability. In this talk I will discuss some of our ongoing efforts in developing next-generation organoids that are assembled by guiding cell-intrinsic self-patterning through engineered stem cell microenvironments. I will also present recent examples of how we are using these engineered organoids for disease modeling, in particular in the area of solid tumors.

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